Effects of CDP-choline and the combination of CDP-choline and galantamine differ in an animal model of schizophrenia: Development of a selective alpha(7) nicotinic acetylcholine receptor agonist strategy.

摘要

The regionally selective reduction of expression of the alpha(7) nicotinic acetylcholine receptor (alpha(7) nAChR) in schizophrenia underlies impaired sensory inhibition, a possible endophenotype of the disorder. This ligand-gated ion channel receptor has been proposed as a pharmacotherapeutic target in schizophrenia. The current study examined the effect of CDP-choline alone and the combination of CDP-choline and galantamine, administered acutely and once-daily for five consecutive days, in an animal model of NMDA receptor hypofunction that is relevant to schizophrenia. The results support the allosteric modulatory influence of galantamine on CDP-choline; however, individual doses of CDP-choline and galantamine must be carefully titrated in order to achieve optimal levels of alpha(7) nAChR "agonism" that may be necessary for the desired therapeutic effect.